Clinical Evidence Concise: A Publication of BMJ Publishing Group

Rheumatoid Arthritis

What are the effects of treatments?

BENEFICIAL

Antimalarials

One systematic review has found that hydroxychloroquine reduces disease activity and joint inflammation compared with placebo in people with rheumatoid arthritis. We found insufficient evidence about effects on functional status. One systematic review found no consistent difference in the effectiveness between antimalarials and other disease-modifying antirheumatic drugs (DMARDs).

Methotrexate

One systematic review has found that methotrexate reduces joint inflammation and radiologic progression, and improves functional status compared with placebo in people with rheumatoid arthritis. One systematic review and subsequent RCTs have found no consistent differences in efficacy between methotrexate versus leflunomide, parenteral gold, or etanercept.

Minocycline

RCTs have found that minocycline improves control of disease activity compared with placebo. We found no RCTs comparing minocycline versus other DMARDs.

Short-Term Low-Dose Oral Corticosteroids

One systematic review has found that low-dose oral corticosteroids taken for several weeks significantly reduce disease activity and joint inflammation compared with placebo.

Sulfasalazine

Systematic reviews have found that sulfasalazine versus placebo for six months significantly reduces disease activity and joint inflammation. We found inadequate evidence on radiologic progression and functional status. One systematic review found no consistent differences between sulfasalazine and other DMARDs. Another systematic review of observational studies and RCTs found that over five years people were less likely to continue sulfasalazine than methotrexate.

LIKELY TO BE BENEFICIAL

Auranofin (Less Effective Than Other DMARDs)

One systematic review has found that auranofin (oral gold) versus placebo reduces disease activity and joint inflammation, but found no evidence on radiologic progression or long-term functional status. Limited evidence from RCTs suggests that auranofin is less effective than DMARDs.

Leflunomide (Long-Term Safety Unclear)

One systematic review has found that leflunomide versus placebo reduces disease activity and joint inflammation, improves functional status and health-related quality of life, and decreases radiologic progression. We found no good evidence on long-term adverse effects. We found no consistent evidence of a difference in clinical efficacy between leflunomide and methotrexate or sulfasalazine.

Treatment with Several DMARDs Combined

One systematic review and subsequent RCTs have found that combining certain DMARDs is more effective than using individual drugs alone. However, the balance between benefit and harm varies among combinations.

Tumor Necrosis Factor Antagonists (Long-Term Safety Unclear)

RCTs have found that tumor necrosis factor antibodies (etanercept and infliximab) significantly improve symptoms, and reduce long-term disease activity and joint inflammation compared with placebo. One RCT found no significant difference between etanercept and methotrexate for quality of life at one year. Short-term toxicity is relatively low, but long-term safety is less clear.

TRADE OFF BETWEEN BENEFITS AND HARMS

Azathioprine

One systematic review has found that azathioprine versus placebo reduces disease activity in the short term (16 weeks to six months). We found no evidence on radiologic progression or long-term functional status. A high level of toxicity limits the usefulness of azathioprine.

Cyclosporin

One systematic review has found that cyclosporin taken for a minimum of four months significantly reduces disease activity and joint inflammation, improves functional status, and may decrease the rate of radiologic progression compared with methotrexate. One RCT found no significant difference between parenteral gold versus cyclosporin for radiologic joint damage or self assessment of change in disease activity at 36 months. A very high frequency of toxicity limits the usefulness of cyclosporin.

Cyclophosphamide

One systematic review has found that cyclophosphamide significantly reduces disease activity and joint inflammation compared with placebo at six months. It also may reduce the rate of radiologic progression, but evidence was limited. We found no evidence of its effect on long-term functional status. Severe toxicity limits its usefulness.

Long-Term Low-Dose Oral Corticosteroids

One systematic review and one subsequent RCT have found that low-dose oral corticosteroids taken for at least three months significantly reduce pain, joint inflammation, and functional status compared with placebo. However, long-term use is associated with considerable adverse effects.

Parenteral Gold

One systematic review has found that parenteral gold reduces disease activity and joint inflammation, and slows radiologic progression compared with placebo in people with rheumatoid arthritis. We found no evidence on long-term functional status. One systematic review and one RCT indicate increased withdrawals because of toxicity. RCTs found no significant differences in clinical efficacy between parenteral gold and methotrexate or cyclosporin at one to three years.

Penicillamine

One systematic review has found that penicillamine reduces disease activity and joint inflammation compared with placebo at four to six months. We found no evidence about effects of penicillamine on radiologic progression or long-term functional status. One systematic review has found no consistent difference between penicillamine versus other DMARDs. Common and potentially serious adverse effects limit the usefulness of penicillamine.

Definition

Rheumatoid arthritis is a chronic inflammatory disorder. It is characterized by a chronic polyarthritis that primarily affects the peripheral joints and related periarticular tissues. It usually starts as an insidious symmetric polyarthritis, often with nonspecific systemic symptoms. Diagnostic criteria include arthritis lasting longer than six weeks (although evidence suggests that 12 weeks is more specific), positive rheumatoid factor, and radiologic damage.1

Incidence/Prevalence

Prevalence ranges from 0.5 to 1.5 percent of the population in industrialized countries.2,3 Rheumatoid arthritis occurs more frequently in women than men (2.5:1).2,3 The annual incidence in women was recently estimated at 36 per 100,000 and in men at 14 per 100,000.3

Etiology/Risk Factors

The evidence suggests that the cause is multi-factorial in people with genetic susceptibility.4

Prognosis

The course of rheumatoid arthritis is variable and unpredictable. Some people experience flares and remissions, and others have a progressive course. Over years, structural damage occurs, leading to articular deformities and functional impairment. About one half of people will be unable to work within 10 years.5 Rheumatoid arthritis shortens life expectancy.6